title: The application of Heck reaction in the synthesis of guaianolide sesquiterpene lactones derivatives selectively inhibiting resistant acute leukemic cells.
abstract: A series of guaianolide-type sesquiterpene lactones derivatives with arylation of α-methylene-γ-lactone moiety was synthesized using Heck reactions, and was evaluated for their activities against acute myelogenous leukemia (AML) cell line HL-60 and doxorubicin-resistant cell line HL-60/A. Although all compounds were significantly less active against HL-60 than the parent molecules, surprisingly, compounds 3a, 4c-4e, 5e, and 8d exhibited high potency against doxorubicin-resistant cell line HL-60/A (IC50=6.2-19 μM), and their activities against HL-60/A were comparable to that of their parent molecules. In view of their novel activities against HL-60/A, compound 5e with inhibitory activity against HL-60/A (IC50=6.2±0.5 μM) was selected for study its preliminary mechanism. The result reveals that compound 5e can obviously induce apoptosis.
authors.affiliation: College of Pharmacy, The State Key Laboratory of Elemento-Organic Chemistry, Synergetic Innovation Center of Chemical Science and Engineering (Tianjin), and Tianjin Key Laboratory of Molecular Drug Research, Nankai University, Tianjin 300071, PR China.
authors.forename: Ya-Hui
authors.initials: YH
authors.lastname: Ding
authors.forename: Hong-Xia
authors.initials: HX
authors.lastname: Fan
authors.forename: Jing
authors.initials: J
authors.lastname: Long
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhang
authors.forename: Yue
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D060326:Chemistry Techniques, Synthetic; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D018922:HL-60 Cells; D006801:Humans; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015470:Leukemia, Myeloid, Acute / Q000188:drug therapy* / Q000473:pathology; D045789:Sesquiterpenes, Guaiane / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D007783:Lactones; D045789:Sesquiterpenes, Guaiane; D004317:Doxorubicin
keywords: Acute myelogenous leukemia; Dehydrocostus lactone; Guaianolide-type sesquiterpene lactones; Micheliolide; Synthesis